Shivani Verma

Nanotechnology: A magic bullet for HIV AIDS treatment

Abstract Human immunodeficiency virus (HIV) infection has become devastating in last a few years. Nearly 7400 new infection cases are coming every day. Highly active antiretroviral therapy (HAART), which involves combination of at least three antiretroviral (ARV) drugs, has been used to extend the life span of the HIV-infected patients. HAART has played an important role to reduce mortality rate in the developed countries but in the developing countries condition is still worst with millions of people being infected by this disease. For the improvement of the situation, nanotechnology-based drug system has been explored for the HIV therapeutics. Nanosystems used for HIV therapeutics offer some unique advantage like enhancement of bioavailability, water solubility, stability, and targeting ability of ARV drugs. Main nanotechnology-based systems explored for HIV therapeutics are liposomes, nanoparticles, niosomes, polymeric micelles, and dendrimers. Present manuscript reviews conventional method of HIV therapeutics and recent advances in the eld of nanotechnology-based systems for treatment of HIV-AIDS.

Exosomes: Natural Carriers for siRNA Delivery

Various cells of the human physiological system have the capability to release extracellular vesicles (EVs) involved in intercellular transport of proteins and nucleic acids. Exosomes are a subtype of extracellular vesicles having their origin through endocytic pathway. While being involved in intercellular transport of macromolecules, exosomes, due to their presence in several body fluids, can also be utilized as a system to commute RNA molecules and proteins in the body. Recent advances in gene therapy have provided a new outlook in disease therapeutics by modulation of gene expression using oligonucleotide based approach and exosomes have been reported a potential carrier for nucleic acid based therapeutic moieties. In recent years, small interfering RNA (siRNA) has emerged as promising therapeutic alternative for diseases with gene-based pathophysiology, however poor bioavailability limits its therapeutic potential. For effective delivery and enhancement of bioavailability of siRNA, several carriers including dendrimers, liposomes, siRNA conjugates, and siRNA aptamer chimeras, to name a few, have been explored. Exosomes can be considered a promising carrier for effective delivery of siRNA due to their existence in bodys endogenous system and high tolerance. The present review focuses on delivering knowledge about exosomes, siRNA, and capability of exosomes to act as natural carriers for siRNA delivery.

Eradication of superficial fungal infections by conventional and novel approaches: a comprehensive review

Abstract During the last two decades, the occurrence of fungal infections either superficial or systemic has been increasing. Moreover, fungal infections become more difficult to treat when they show coupling with immunogenic diseases like AIDS. Superficial fungal infections are associated with skin, nail and eye and are less prominent to systemic infection. However, it may be dangerous if not treated properly. It is usually observed that conventional formulations including cream, powder, gels etc. are used to treat skin fungal infections even for the deep seated fungal infections. However, these formulations show various side-effects on the application site like burning, redness and swelling. Further, due to the immediate release of drug from these formulations they can stimulate the immune system of body generating high impact allergic reactions. Deep seated fungal infections like invasive aspergillosis and invasive candidiasis may be more difficult to treat because the drug released from conventional topical formulation can not reach at the target site due to the low penetration capacity. Similarly, in case of fungal infection of nail and eye, conventional formulations show problem of less bioavailability. Thus, to overcome the drawbacks of conventional therapy a lot of research works have been carried out to develop novel formulations of antifungal drugs to deliver them superficially. Novel formulations explored for the skin delivery of antifungal drugs include liposomes, niosomes, ethosomes, microemulsions, nanoparticles, microspheres and micelles. These formulations show extended or sustained release of drug, minimizing the side effect on application site, enhancing bioavailability and reducing the dosing frequency. Further, these formulations also show penetration into the deep skin to treat invasive fungal infections. Novel formulations explored in treatment of fungal infections of eye are liposomes and nanoparticles and whether for nail fungal infections microemulsions are the choice. In present article, we have discussed about conventional treatment of superficial fungal infection and their comparison with the novel drug delivery systems.

Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization.

Abstract Cutaneous candidiasis is a common topical fungal infection which may be more prominent in patients associated with AIDS. It is usually treated by conventional formulations such as cream, gel, which show various adverse effects on skin along with systemic absorption. To overcome these drawbacks, various novel drug delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based microparticulate systems have shown good dermal penetration after topical application. Therefore, in the present study clotrimazole-loaded PLGA microspheres were prepared for targeted dermal delivery. Microspheres were prepared by using a single emulsification (oil-in-water, O/W) evaporation technique and characterized for different parameters. Prepared microparticulate systems were dispersed in Carbopol 934® gel and antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed guinea pigs. Particle size of optimized formulation was 2.9 µm along with 74.85% entrapment of drug. Skin retention studies revealed that drug accumulation in the skin was higher with microspheres gel as compared to marketed gel. Confocal microscopy of skin further confirmed penetration of microspheres up to 50 µm into the dermal region. In-vivo antifungal activity studies demonstrated that microsphere gel showed better therapeutic activity, lowest number of cfu/ml was recorded, as compared to marketed gel after 96 h of application. Based on the results of the study, it can be concluded that PLGA microparticles may be promising carriers to deliver clotrimazole intradermally for the treatment of invasive fungal infections.

Mercapto functionalized silica entrapped polyacrylamide hydrogel: Arsenic adsorption behaviour from aqueous solution

In this article, 3-mercaptopropyl functionalized silica entrapped polyacrylamide hydrogel (MPFS-PAA) was prepared and characterized by FT-IR, scanning electron microscopy (SEM) and energy dispersion X-ray spectroscopy (EDS). Synthesized hydrogel was evaluated for removal of arsenic(III) from aqueous solution. Adsorption studies were carried out by batch method as function of contact time, initial concentration of arsenic and pH. As(III) adsorption data fitted well with Langmuir and Freundlich isotherm models. Adsorption capacity of arsenic 92.5 μg/g was obtained at initial concentration of 100 μg/L by Langmuir isotherm. Adsorption kinetics was tested for pseudo-second order reaction at different contact time. The rate constants of pseudo second order reaction were calculated and good correlation coefficient R(2) 99.67 obtained. The results indicates that MPFS-PAA is an effective adsorbent for removal of As(III) from aqueous solution.

Fatty acid vesicles acting as expanding horizon for transdermal delivery.

Abstract The body is protected against the external environment by the skin due to its physical barrier nature. Stratum corneum composed of corneocytes surrounded by lipid region performs a major barrier function as it lies in the uppermost area of skin. Alteration in barrier function, increase in permeability, and disorganization of stratum corneum represent diseased skin. Drugs applied to the diseased skin should induce a local effect at the site of application or area close to it along with cutaneous absorption rather than percutaneous absorption. Conventional formulations like ointments, gels, and creams suffer from the drawback of limited local activity. For the enhancement of drug penetration and localization of the drug at the site of action approaches explored are liposomes, niosomes, ethosomes microparticles, and solid lipid nanoparticles. Vesicles composed of fatty acids like oleic acid and linoleic acid represent the new approach used for transdermal penetration and localization. In this review article, our major aim was to explore the applications of fatty acid vesicles for transdermal delivery of various bioactives.

Liposomes for the delivery of streptokinase

Streptokinase is an efficient thrombolytic agent used to treat thromboembolic disorders. Conventional streptokinase formulations have limited thrombolytic activity and several shortcomings because of their immunogenicity and dose-related side effects including short half-life, lack of tissue targeting and peripheral bleeding. Different liposomal formulations have been explored by researchers in order to improve thrombolytic activity of streptokinase. Liposomal formulations could improve plasma stability, retain drug for longer periods of time in the circulation and promote selective delivery to the thrombus. Side effects of conventional streptokinase formulations, such as immunogenicity and hemorrhage, can also be reduced by using liposomal carriers. In vivo therapeutic efficacy of the liposomal streptokinase has been demonstrated well in animal models. In the present review, we will discuss the potential of different liposomal carriers to improve thrombolytic efficacy of streptokinase.

Transethosomes Of Econazole Nitrate For Transdermal Delivery: Development, In-Vitro Characterization, And Ex-Vivo Assessment

BACKGROUND Transdermal drug delivery is an attractive approach for both local and systemic therapeutics of various diseases. Transdermal drug delivery systems show various advantages like reduction of local irritation, prevention of first-pass hepatic metabolism, and bioavailability enhancement of bioactive molecules over conventional drug delivery systems. OBJECTIVE The main objective of the present research work was to develop and characterize (in-vitro and ex-vivo) econazole nitrate loaded transethosomes and their comparison with marketed cream of econazole nitrate [Ecoderm, Brown and Burk Pharmaceutical (Pvt.) Ltd., Bengaluru, India] for effective transdermal delivery. METHOD Transethosomes loaded with econazole nitrate were developed by homogenization method and evaluated for entrapment (%), vesicular size, zeta potential, polydispersity index (PDI), and invitro drug release. Furthermore, optimized econazole nitrate loaded transethosomes were added to Carbopol 934 gel and this gel was evaluated for viscosity, pH, drug content, ex-vivo skin permeation and retention studies followed by in-vitro antifungal activity against C. albicans fungus. RESULTS The optimized transethosomes loaded with econazole nitrate showed vesicle size of 159.3 ± 4.3 nm, entrapment efficiency about 78.3 ± 2.8%, acceptable colloidal properties like (zeta potential = -27.13 ± 0.33 mV, PDI = 0.244 ± 0.045), approximately 57.56 ± 2.33% drug release up to 24 h. Results of DSC analysis confirmed the encapsulation of econazole nitrate inside transethosomes. Optimized transethosomes showed drug release following zero order through diffusion mechanism. Transethosomal gel showed high drug content (92.35 ± 0.63%) and acceptable values of pH (5.68 ± 0.86) or viscosity (10390 ± 111 cPs). Transethosomal gel showed less ex-vivo skin penetration (17.53 ± 1.20%), high ex-vivo skin retention (38.75 ± 2.88%), and high in-vitro antifungal activity compared to the marketed cream of econazole nitrate. CONCLUSION Therefore, it can be concluded that econazole nitrate loaded transethosomes are effective to deliver econazole nitrate transdermally in a controlled fashion for effective elimination of cutaneous candidiasis.

Exploring Therapeutic Potential of Nanocarrier Systems Against Breast Cancer

BACKGROUND Breast cancer is the most widely occurring non-cutaneous cancer in women. Treatment options available for breast cancer are limited and there are a number of toxicity concerns associated with them. Therefore, nanocarrier based approaches have been explored for breast cancer treatment. Nanocarriers implemented for breast cancer treatment are nanoliposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, dendrimers, and protein nanocages. OBJECTIVE Objective of this review was to explore the therapeutic efficacy of various nanocarrier systems against breast cancer. METHOD Existing literature regarding nanocarrier systems for breast cancer therapy was reviewed using Pubmed and Google Scholar. RESULTS Nanocarriers may show prolonged circulation time of chemotherapeutic agent with efficient breast tumor targeting. Both active and passive targeting methodologies can be explored to target breast cancer cells using different nanocarriers. Targeted nanocarriers have the capability to reduce side effects caused by various conventional formulations used to treat breast cancer. CONCLUSION Various nanocarriers listed above have shown their therapeutic potential in preclinical studies to treat breast cancer. Satisfactory clinical evaluation and scale up techniques can promote their entry into the pharmaceutical market in greater extent.

Advanced Drug Delivery Systems for Transdermal Delivery of Non- Steroidal Anti-Inflammatory Drugs: A Review

BACKGROUND Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first-pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarriers explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers. OBJECTIVES In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. CONCLUSIONS Advanced nanocarriers have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge.